In vivo evidence for a prodrug activation mechanism during colibactin maturation

Chembiochem. 2013 Jul 8;14(10):1194-7. doi: 10.1002/cbic.201300208. Epub 2013 Jun 6.

Abstract

Releasing the cytopath: We have identified an N-myristoyl-D-asparagine (1) as the free N-terminal prodrug scaffold in cytopathogenic Escherichia coli strains expressing the colibactin gene cluster. Colibactin is released in vivo upon cleavage of precolibactin. We provide for the first time in vivo evidence of the prodrug-like release mechanism of colibactin.

Keywords: E. coli Nissle; biosynthesis; colibactin; gene expression; prodrug maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Multigene Family
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism*
  • Polyketides / chemistry
  • Polyketides / metabolism*
  • Prodrugs / pharmacokinetics*

Substances

  • Peptides
  • Polyketides
  • Prodrugs
  • colibactin